Project Abstract eMERGE IV (E4) proposes to investigate the implementation of 15 ?genomic risk assessment? (GRA) scores in a network-wide set of diverse participants. These GRAs will include polygenic risk score (PRS) information, as well as risk information, such as personal and family health history, environmental and social health determinants, and physical and lab measures. The GRA will aggregate these factors into a single score to identify those who would benefit from screening and other interventions. Substantial challenges must be addressed before genomic medicine is a part of standard medical care. We will collaborate to refine multi-ancestry GRAs and support the inclusion of non-genetic risk factors extracted from the electronic health record with innovative natural language processing approaches and apply them in a cohort enriched for Asian ancestry, and sexual and gender minorities. The specific aims of our proposal are designed to use an implementation science approach to advance the integration of genomic data into clinical practice, including evaluation of patient perspectives and economic outcomes, and broadening the impact of eMERGE through collaborations. The University of Washington Medicine dedication to preventative health in a learning health system and broad expertise across genomics, statistical, ethical, informatic, implementation, outcomes and economic disciplines will support this multi-site clinical trial. Specific Aims: Aim 1: Refine GRA scores and outcomes measures for five high impact conditions, considering stakeholder input, for implementation in the electronic health record. The conditions are: colorectal cancer, breast cancer, osteoporosis, coronary artery disease, and glaucoma. Aim 2: Integrate 15 GRA scores and electronic clinical decision support for management into clinical care and the EHR and capture clinical outcomes. Aim 3: Evaluate the implementation, effectiveness, and economic utility of GRA result return.